Cryosurgery is a treatment modality that is currently used by various specialists to treat benign and malignant neoplasms. It has been shown to be effective in the destruction of local lesions. Recent reports indicate that cryosurgery may also have beneficial effects on the host with malignant disease by increasing the immunity of the host. In this proposal we will continue to study the local effects of freezing of normal tissues and tumors by various techniques. Particular emphasis will be placed on the vascular changes in the cryolesion. We will extend the studies to include the effects of cryosurgery on treatment of malignant disease at the local site, and also on the progress of secondary disease using the B16 mouse melanoma model. The effects of the treatment of the primary lesion with cryosurgery will be determined: 1) on establishment of concomitant tumors in early, intermediate and late stages of disease; 2) on progression of established metastatic lesions; 3) on survival time in experiments using combination therapy. The effects of cryosurgery will be compared with excisional surgery in order to determine the progression of secondary disease. These studies are necessary for delineating the future role of cryosurgery in treatment of human malignant disease.